FDA Expands Use of Incyte’s Jakafi to Include GVHD

The U.S. Food and Drug Administration expanded the approval for Incyte’s Jakafi to include chronic graft-versus-host disease after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.

Photo: Steven Stein, chief medical officer of Incyte

GVHD is a condition that can occur after an allogeneic stem cell transplant (the transfer of stem cells from a donor) in which the donated cells initiate an immune response and attack the transplant recipient’s organs. There are two major forms of GVHD: acute, which generally occurs within 100 days of transplant, and chronic, which generally occurs more than 100 days after transplant. Both forms are associated with significant morbidity and mortality and can affect multiple organ systems.

Jakafi is a JAK1/JAK2 inhibitor. The FDA previously approved Jakafi for the treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea, intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF in adults. Jakafi is marketed by Novartis as Jakavi outside the United States.

“GVHD is the leading cause of morbidity and mortality in patients following an allogeneic stem cell transplant, yet there historically have been limited treatment options available beyond first-line systemic therapies,” stated Steven Stein, chief medical officer of Incyte.

The FDA approval was based on the REACH3 study, a phase 3, randomized, open-label, multicenter study of Jakafi in comparison to best available therapy (BAT) for treatment of steroid-refractory chronic GVHD after allogeneic stem cell transplantation. The primary endpoint of overall response rate (ORR) at Week 24 (Cycle 7 Day 1) was 49.7 percent for Jakafi compared to 25.6 percent for BAT. Furthermore, the ORR through Cycle 7 Day 1 was 70 percent for Jakafi compared to 57 percent for BAT.

The most common hematologic adverse reactions (incidence > 35 percent) were anemia and thrombocytopenia. The most common nonhematologic adverse reactions (incidence ≥ 20 percent) were infections (pathogen not specified) and viral infection. Full results from the REACH3 study were published in the New England Journal of Medicine.

“Nearly half of the people who develop chronic GVHD do not respond adequately to steroids – the current standard of care – making this life-threatening condition particularly challenging to treat,” said Robert Zeiser, University Medical Center Freiburg, Department of Hematology, Oncology and Stem Cell Transplantation, Freiburg, Germany, the principal investigator of the REACH3 trial. “In this clinical trial, treatment with Jakafi demonstrated significantly improved outcomes across a range of efficacy measures compared to best available therapy. This approval represents a significant advancement in the treatment of appropriate patients with chronic GVHD – for both the patients who face a poor prognosis and the healthcare providers who struggle to effectively treat them.”

Author: Rare Daily Staff